Acute subjective sensory perceptions predict relative reinforcing effects of smoked nicotine

A recent study demonstrated that during a single sampling period, 0.1 mg of intravenous (IV) nicotine (vs. placebo) was found to be the threshold for subjective and physiological drug effects. The present study is a secondary analysis evaluating whether the threshold for subjective and physiological effects is similar when the subject has repeated opportunities to choose blinded doses of nicotine versus placebo. We also examined whether cigarette craving, withdrawal, and rate of nicotine metabolism affected nicotine reinforcement, defined by a greater number of nicotine choices than placebo. Young adult (n = 34; 68% male), daily smokers had five laboratory sessions after overnight abstinence. After sampling an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg/70 kg) versus saline (placebo), participants completed a nicotine self-administration (NSA) procedure that included 10 opportunities to self-administer IV dose of nicotine or placebo. The threshold for subjective positive effects of nicotine during the NSA was equal to or lower than the sampling period, 0.05-0.1 mg versus 0.1 mg. The threshold for nicotine-induced heart rate increase was higher during the NSA than during the sampling period (0.2 mg vs. 0.1 mg). Higher baseline craving and nicotine metabolite ratio (NMR) were associated with nicotine reinforcement at 0.2 mg and 0.1 mg doses, respectively ( p < .05). The results suggest that subjective effects during NSA are reported at doses lower than the sampling period. Taken together, tobacco products thought to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects. Public Health SignificanceIn young adult nondependent smokers, the threshold for positive subjective effects of nicotine was 2-4 times lower than its reinforcing threshold (0.05-0.1 mg vs. 0.2 mg) during a nicotine self-administration procedure. Additionally, higher abstinence-induced craving and faster nicotine metabolism were associated with greater reinforcement from nicotine. A four times lower threshold for the subjective pleasurable effects than the reinforcing effects of nicotine suggests that tobacco products that are deemed to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects.

Section: Discussionmentioning

confidence: 99%

Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration.

MacLean¹,

Eid²,

Parida³

et al. 2023

“…Chi-square tests and Fisher’s exact tests were used to identify differences in baseline characteristics between exclusive and dual users. For each PRT outcome, differences between experimental ENDS conditions and the OB ENDS condition were assessed using mixed effects linear regressions with robust standard errors, a flexible and efficient approach (Gueorguieva & Krystal, 2004) that has been used in other studies comparing the abuse liability of tobacco products (Barnes et al, 2017; Bono et al, 2020; Karelitz & Perkins, 2021). Pairwise differences between each experimental ENDS condition were then assessed with Wald tests.…”

Section: Methodsmentioning

confidence: 99%

The interaction of nicotine concentration and device power on electronic nicotine delivery system (ENDS) abuse liability among exclusive ENDS users and dual users of ENDS and combustible cigarettes.

Hoetger¹,

Bono²,

White³

et al. 2022

Open-system electronic nicotine delivery systems (ENDS) permit modifications to device characteristics such as power, potentially increasing nicotine and toxicant delivery. Limiting liquid nicotine concentration may carry unintended consequences by prompting users to increase device power to increase nicotine delivery. This study examined the abuse liability of ENDS across nicotine concentration and power settings. In a clinical laboratory study, n = 19 exclusive ENDS users and n = 13 dual ENDS/cigarette users, aged 21-55 completed four Latin-square ordered conditions that varied by liquid nicotine concentration (10 mg/ ml [low], 30 mg/ml [high]) and device power (15 watts [low], 30 watts [high]), that were followed by a fifth own brand (OB) condition. A progressive ratio task (PRT) using bar presses to earn ENDS puffs was used to assess abuse liability and compare between conditions using mixed effects linear regressions. The low played equal role in conceptualization, data curation, funding acquisition, investigation, methodology, project administration, resources, supervision, validation and writing of review and editing. Caroline O. Cobb played equal role in conceptualization, data curation, funding acquisition, investigation, methodology, project administration, resources, supervision, validation and writing of review and editing.

“…For example, to further validate the ACP (Perkins, Karelitz, & Kunkle, 2018), we found that the greater the subsequent choice of a 17 mg/g nicotine Spectrum cigarette versus the 0.4 mg/g VLNC, the greater the difference in these ACP ratings during initial exposure to each cigarette. A more recent and better controlled study found that the difference in ACP between the full range of cigarettes higher in nicotine, each versus the VLNC, predicted the magnitude of that subsequent greater preference for the higher nicotine cigarette in the choice procedure (Karelitz & Perkins, 2020). This is consistent with our understanding of drug preference, that choice is driven by the immediate pleasurable effects that drug condition elicits.…”

Section: Research On Behavioral Discrimination Of Nicotine Via Cigare...mentioning

confidence: 99%

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Perkins¹

2022

Self Cite

This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins’s American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author’s initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine’s neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine’s self-reported “reward” and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration’s efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use.